Effect of mild hypothermia on activity of hippocampal protein kinase R-like endoplasmic reticulum kinase in a mouse model of cerebral ischemia-reperfusion

Abstract

Objective To evaluate the effect of mild hypothermia on the activity of hippocampal protein kinase R-like endoplasmic reticulum kinase (PERK) in a mouse model of cerebral ischemia-reperfusion (I/R). Methods One hundred and twenty male C56BL6 mice, weighing 20-30 g, aged 7 weeks, were randomly divided into 3 groups (n=40 each) using a random number table: sham operation group (group S), I/R group, and mild hypothermia group (group H). Cerebral I/R was induced by occlusion of bilateral common carotid arteries for 15 min followed by reperfusion in anesthetized mice.In group H, surface cooling was performed immediately after reperfusion, and the rectal temperature was maintained at 32-34 ℃ for 3 h. In I/R and S groups, the rectal temperature was maintained at 36.8-37.2 ℃.At 6, 12, 24 and 72 h of reperfusion, 10 mice were sacrificed in each group, and the hippocampi were removed for determination of the number of apoptotic neurons in hippocampal CA1 region(by TUNEL), and phosphorylated PERK(p-PERK) expression (by Western blot). Results Compared with group S, the number of apoptotic neurons was significantly increased, and the expression of p-PERK was up-regulated at each time point in I/R and H groups (P<0.05). Compared with group I/R, the number of apoptotic neurons was significantly decreased, and the expression of p-PERK was down-regulated at each time point in group H (P<0.05). Conclusion Mild hypothermia can reduce endoplasmic reticulum stress through inhibiting hippocampal PERK activity, thus attenuating cerebral injury in a mouse model of cerebral I/R. Key words: Hypothermia, induced; Reperfusion injury; Brain; Endoplasmic reticulum stress; Hippocampus